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脊髓 GLP-1 受体信号转导的治疗潜力。

Therapeutic potential of spinal GLP-1 receptor signaling.

机构信息

Department of Orthopaedics, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.

Department of Orthopaedics, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.

出版信息

Peptides. 2018 Mar;101:89-94. doi: 10.1016/j.peptides.2018.01.003. Epub 2018 Jan 9.

Abstract

GLP-1 signaling pathway has been well studied for its role in regulating glucose homeostasis, as well as its beneficial effects in energy and nutrient metabolism. A number of drugs based on GLP-1 have been used to treat type 2 diabetes mellitus. GLP-1R is expressed in multiple organs and numerous experimental studies have demonstrated that GLP-1 signaling pathway exhibits pro-survival functions in various disorders. In the central nervous system, stimulation of GLP-1R produces neuroprotective effects in specific neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. The preproglucagon neurons located in the brainstem can also produce GLP-1. GLP-1 analogs have a long-acting effect and are able to pass the blood-brain barrier, which probably extends the therapeutic efficacy of GLP-1R activation. Neurodegenerative or traumatic conditions can damage the spinal cord and result in motor and sensory dysfunction. Evidence supports that GLP-1R activation in the spinal cord possesses beneficial effects and significant therapeutic potential. Herein, we review studies that have focused on GLP-1 and the spinal cord, and summarize the expression of GLP-1R and the innervation of PPG neurons in the spinal cord, as well as the potential therapeutic benefits of GLP-1R activation.

摘要

GLP-1 信号通路在调节葡萄糖稳态以及在能量和营养代谢方面的有益作用已得到深入研究。许多基于 GLP-1 的药物已被用于治疗 2 型糖尿病。GLP-1R 在多个器官中表达,许多实验研究表明,GLP-1 信号通路在各种疾病中表现出促生存功能。在中枢神经系统中,GLP-1R 的刺激在特定的神经退行性疾病中产生神经保护作用,如阿尔茨海默病和帕金森病。位于脑干的前胰高血糖素原神经元也可以产生 GLP-1。GLP-1 类似物具有长效作用并且能够穿过血脑屏障,这可能延长 GLP-1R 激活的治疗效果。神经退行性或创伤性疾病会损伤脊髓,导致运动和感觉功能障碍。有证据表明,脊髓中 GLP-1R 的激活具有有益作用和显著的治疗潜力。本文综述了聚焦于 GLP-1 和脊髓的研究,总结了 GLP-1R 在脊髓中的表达和 PPG 神经元的神经支配,以及 GLP-1R 激活的潜在治疗益处。

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